Negative Molecular Diagnostics in Non-Syndromic Hearing Loss: What Next?

Clabout, Thomas; Maes, Laurence; Acke, Frederic; Wuyts, Wim; Schil, Kristof Van; Coucke, Paul; Janssens, Sandra; Leenheer, Els De

doi:10.3390/genes14010105

Cited by 3 publications

(3 citation statements)

References 34 publications

(46 reference statements)

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“…Some genes or variants are difficult to assay using current NGS and bioinformatic methods. For example, the F8 gene has a common inversion and the STRC gene has a near-identical pseudogene, pSTRC [ 50 ], which makes these genes more difficult to analyze. In two recent studies, NC NEXUS and NBSeq, the sensitivity of WES gNBS was comparatively high for IEM (88%), similar to that modeled by Kingsmore et al, for other genetic conditions [ 26 ], compared to a mere 18% for newborns with hearing loss conditions [ 49 , 96 ].…”

Section: Genomic Approaches For Nbsmentioning

confidence: 99%

The Multi-Omic Approach to Newborn Screening: Opportunities and Challenges

Ashenden,

Chowdhury,

Anastasi

et al. 2024

IJNS

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Newborn screening programs have seen significant evolution since their initial implementation more than 60 years ago, with the primary goal of detecting treatable conditions within the earliest possible timeframe to ensure the optimal treatment and outcomes for the newborn. New technologies have driven the expansion of screening programs to cover additional conditions. In the current era, the breadth of screened conditions could be further expanded by integrating omic technologies such as untargeted metabolomics and genomics. Genomic screening could offer opportunities for lifelong care beyond the newborn period. For genomic newborn screening to be effective and ready for routine adoption, it must overcome barriers such as implementation cost, public acceptability, and scalability. Metabolomics approaches, on the other hand, can offer insight into disease phenotypes and could be used to identify known and novel biomarkers of disease. Given recent advances in metabolomic technologies, alongside advances in genomics including whole-genome sequencing, the combination of complementary multi-omic approaches may provide an exciting opportunity to leverage the best of both approaches and overcome their respective limitations. These techniques are described, along with the current outlook on multi-omic-based NBS research.

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Section: Genomic Approaches For Nbsmentioning

confidence: 99%

The Multi-Omic Approach to Newborn Screening: Opportunities and Challenges

Ashenden,

Chowdhury,

Anastasi

et al. 2024

IJNS

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show abstract

“…Many pathogenic variants affecting known deafness genes may go undetected using current diagnostic algorithms because they reside in non-coding (intronic and regulatory) sequences or unannotated exons [ 304 ]. Therefore, consideration should be given to implementing whole exome or whole genome sequencing with a virtual panel as the gold standard for genetic testing in HL instead of targeted gene sequencing panels [ 305 ].…”

Section: Autosomal Dominant Non-syndromic Hearing Loss (Dfna)mentioning

confidence: 99%

Autosomal Dominant Non-Syndromic Hearing Loss (DFNA): A Comprehensive Narrative Review

et al. 2023

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Autosomal dominant non-syndromic hearing loss (HL) typically occurs when only one dominant allele within the disease gene is sufficient to express the phenotype. Therefore, most patients diagnosed with autosomal dominant non-syndromic HL have a hearing-impaired parent, although de novo mutations should be considered in all cases of negative family history. To date, more than 50 genes and 80 loci have been identified for autosomal dominant non-syndromic HL. DFNA22 (MYO6 gene), DFNA8/12 (TECTA gene), DFNA20/26 (ACTG1 gene), DFNA6/14/38 (WFS1 gene), DFNA15 (POU4F3 gene), DFNA2A (KCNQ4 gene), and DFNA10 (EYA4 gene) are some of the most common forms of autosomal dominant non-syndromic HL. The characteristics of autosomal dominant non-syndromic HL are heterogenous. However, in most cases, HL tends to be bilateral, post-lingual in onset (childhood to early adulthood), high-frequency (sloping audiometric configuration), progressive, and variable in severity (mild to profound degree). DFNA1 (DIAPH1 gene) and DFNA6/14/38 (WFS1 gene) are the most common forms of autosomal dominant non-syndromic HL affecting low frequencies, while DFNA16 (unknown gene) is characterized by fluctuating HL. A long audiological follow-up is of paramount importance to identify hearing threshold deteriorations early and ensure prompt treatment with hearing aids or cochlear implants.

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“…Chromosome 15 includes several genes involved in spermatogenesis, such as cation channel sperm-associated protein (CATSPER) and the related sensorineural hearing loss (STRC). Translocations in these genetic portions due to OS are correlated with a lack of sperm motility, and therefore infertility, and are also associated with hearing loss [22][23][24].…”

Section: Introductionmentioning

confidence: 99%

Oxidative Stress Biomarkers in Male Infertility: Established Methodologies and Future Perspectives

Mottola,

Palmieri,

Carannante

et al. 2024

Genes

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Male fertility can be affected by oxidative stress (OS), which occurs when an imbalance between the production of reactive oxygen species (ROS) and the body’s ability to neutralize them arises. OS can damage cells and influence sperm production. High levels of lipid peroxidation have been linked to reduced sperm motility and decreased fertilization ability. This literature review discusses the most commonly used biomarkers to measure sperm damage caused by ROS, such as the high level of OS in seminal plasma as an indicator of imbalance in antioxidant activity. The investigated biomarkers include 8-hydroxy-2-deoxyguanosine acid (8-OHdG), a marker of DNA damage caused by ROS, and F2 isoprostanoids (8-isoprostanes) produced by lipid peroxidation. Furthermore, this review focuses on recent methodologies including the NGS polymorphisms and differentially expressed gene (DEG) analysis, as well as the epigenetic mechanisms linked to ROS during spermatogenesis along with new methodologies developed to evaluate OS biomarkers. Finally, this review addresses a valuable insight into the mechanisms of male infertility provided by these advances and how they have led to new treatment possibilities. Overall, the use of biomarkers to evaluate OS in male infertility has supplied innovative diagnostic and therapeutic approaches, enhancing our understanding of male infertility mechanisms.

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Negative Molecular Diagnostics in Non-Syndromic Hearing Loss: What Next?

Cited by 3 publications

References 34 publications

The Multi-Omic Approach to Newborn Screening: Opportunities and Challenges

The Multi-Omic Approach to Newborn Screening: Opportunities and Challenges

Autosomal Dominant Non-Syndromic Hearing Loss (DFNA): A Comprehensive Narrative Review

Oxidative Stress Biomarkers in Male Infertility: Established Methodologies and Future Perspectives

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